The role of diversity in data‐driven analysis of multi‐subject fMRI data: Comparison of approaches based on independence and sparsity using global performance metrics

Data‐driven methods have been widely used in functional magnetic resonance imaging (fMRI) data analysis. They extract latent factors, generally, through the use of a simple generative model. Independent component analysis (ICA) and dictionary learning (DL) are two popular data‐driven methods that are based on two different forms of diversity—statistical properties of the data—statistical independence for ICA and sparsity for DL. Despite their popularity, the comparative advantage of emphasizing one property over another in the decomposition of fMRI data is not well understood. Such a comparison is made harder due to the differences in the modeling assumptions between ICA and DL, as well as within different ICA algorithms where each algorithm exploits a different form of diversity. In this paper, we propose the use of objective global measures, such as time course frequency power ratio, network connection summary, and graph theoretical metrics, to gain insight into the role that different types of diversity have on the analysis of fMRI data. Four ICA algorithms that account for different types of diversity and one DL algorithm are studied. We apply these algorithms to real fMRI data collected from patients with schizophrenia and healthy controls. Our results suggest that no one particular method has the best performance using all metrics, implying that the optimal method will change depending on the goal of the analysis. However, we note that in none of the scenarios we test the highly popular Infomax provides the best performance, demonstrating the cost of exploiting limited form of diversity.     

鼻唇沟微笑切口入路在后颊癌根治术中的应用

目的 探讨应用鼻唇沟微笑切口入路进行后颊癌根治手术的可行性并评价其临床效果。方法 选取2016年8月—2017年3月间行手术治疗的23例后颊癌患者,完成颈部淋巴结清扫术后,在口角外1 cm处的鼻唇沟内设计切口线,即微笑切口。切口呈弧形,向上至鼻翼外下缘,向下与颈淋巴清扫术切口连续。结果 23例患者的原发灶术中显露满意,切缘肿瘤细胞均为阴性。术后随访12~22个月,平均16.5个月,所有患者恢复良好,未见肿瘤复发及远处转移。开口度基本恢复正常,面部切口仅在鼻唇沟处遗留隐蔽的类似“微笑”样的瘢痕。结论 经鼻唇沟微笑切口入路切除后颊癌,术野显露满意,手术操作便利,在不影响肿瘤根治的前提下避免了对患者口裂完整性的破坏,有助于患者开口度的恢复,切口瘢痕隐蔽,值得临床推广应用。     

Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological,pathological and genetic studies of a Taiwanese family

The objective of this study was to assess peripheral nerve involvement and DNA mutation of the neurofibromatosis type 2 (NF2) gene (NF2) in a Taiwanese family with classic NF2. Eleven members (six symptomatic and five asymptomatic) of a family carrying NF2 underwent clinical examination, neuroimaging, and electrophysiological analysis. Mutation and linkage analyses were conducted on DNA samples prepared from peripheral blood (all individuals), a sural nerve biopsy specimen (one symptomatic member), and a tumor specimen (another symptomatic member). Six of the 11 members were diagnosed with classic NF2. DNA sequencing of the tumor specimen demonstrated a frameshift mutation with 756delC on exon 8 of NF2. Three affected subjects showed clinical variability of the neuropathic disorders. Electrophysiological studies demonstrated variation in the disease pattern and severity of peripheral nerve involvement in five affected subjects. The morphometric assessment of the sural nerve biopsy specimen showed a marked reduction in both large myelinated and unmyelinated fibre density and increased density of non‐myelinating Schwann cell nuclei. Apart from numerous pathological nuclei of isolated Schwann cells, multiple profiles of non‐myelinating Schwann cell subunits were apparent in the endoneurium. Schwann cell proliferation in association with first‐hit mutation of the merlin gene might be responsible for the NF2‐associated neuropathy. Sural nerve biopsy showed a progressive neuropathy in the disease. Further, we suggest nonmyelinating Schwann cells are involved in NF2 neuropathy.     

Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: Associated with loss of function of Nav1.1

Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α‐subunit type‐1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. Methods: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high‐performance liquid chromatography (dHPLC) and sequencing. Whole‐cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Na_v1.1 in tsA201 cells. Results: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Na_v1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED‐induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. Conclusions: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Na_v1.1, which may be the basis of seizure aggravation by sodium channel–blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.     

Role of MEK‐ERK pathway in morphine‐induced conditioned place preference in ventral tegmental area of rats

A major goal of research on drug addiction is to develop the effective treatments to deal with the long‐term behavioral disorders especially reinstatement induced by the addictive drugs such as opiates, cocaine, and cannabinoid. The molecular mechanisms underlying these substance‐related disorders remain unclear so far. Here we used the model of morphine‐induced conditioned place preference (CPP) in rats to mimic the progress of drug‐taking, withdrawal and relapse in human. The tissue of ventral tegmental area (VTA), one of the most important brain structures associated with abused drug‐related disorders, was taken and two‐dimensional electrophoresis (2‐DE) was performed to analyze and compare the changes of protein expression patterns during the different stages of morphine‐induced CPP. First, we found that there were 80 proteins identified to be changed in the process of morphine‐induced CPP. Furthermore, as the mitogen‐activated protein kinase kinase 1 (MAPKK1) was increased significantly in the stages of establishment and reinstatement, we confirmed the change of activated extracellular signal‐regulated kinase (ERK) by Western blotting in VTA tissue and cultured cell. The results demonstrated that the activated MEK‐ERK pathway by chronic morphine treatment in VTA was involved in morphine‐induced reinstatement. Moreover, inhibition of MEK‐ERK pathway by infusion the MEK inhibitor U0126 in VTA blocked the establishment of morphine‐induced CPP. The present study found significant changes in a group of protein expressions in VTA during morphine‐induced CPP and further confirmed the role of MEK‐ERK cell signaling pathway of VTA in morphine addiction. © 2010 Wiley‐Liss, Inc.     

高通量透析膜对C-反应蛋白及血脂代谢的影响

背景：传统低通量透析不能改善微炎症状态和脂质代谢紊乱,新型的高通量透析则可以很好的改善这种微炎症状态和脂质代谢,有助于提高患者的生活质量和存活率,因此如何改善微炎症状态和脂质代谢成为人们研究的热点。 目的：观察高通量和低通量聚砜膜血液透析器对维持性血液透析患者血浆超敏C-反应蛋白及血脂代谢的影响。 方法：将44例维持性血液透析患者随机分为高通量透析组和低通量透析组,另选22例健康体健者作为正常对照组。高通量透析组使用高通量透析器FX60,低通量透析组使用低通量透析器F6,均每周透析3次,每次透析4 h;治疗1年后,分别比较两组患者治疗前后及与正常对照组的血超敏C-反应蛋白与总胆固醇、三酰甘油及低密度脂蛋白胆固醇等指标的变化。 结果与结论：两组治疗前血浆超敏C-反应蛋白与三酰甘油、总胆固醇及低密度脂蛋白胆固醇水平均高于正常对照组(P < 0.05);治疗后高通量透析组患者的血浆超敏C-反应蛋白与总胆固醇、三酰甘油及低密度脂蛋白胆固醇水平明显下降(P < 0.05),而低通量透析组无明显变化(P > 0.05)。结果提示采用高通量FX60聚砜膜透析器进行透析能改善维持性透析患者的微炎症状态及脂质代谢。 关键词：高通量透析;血液透析膜;血浆超敏C-反应蛋白;血脂;膜材料 doi:10.3969/j.issn.1673-8225.2010.25.032     

Examining the Role of Race,Ethnicity, and Gender on Social and Behavioral Ratings Within the Autism Diagnostic Observation Schedule

The Autism Diagnostic Observation Schedule (ADOS) is widely used to assess symptoms of autism spectrum disorder (ASD). Given well-documented differences in social behaviors across cultures, this study examined whether item-level biases exist in ADOS scores across sociodemographic groups (race, ethnicity, and gender). We examined a subset of ten ADOS items among participants (N?=?2458). Holding level of overall ADOS behavioral symptoms constant, we found significant item level bias (measurement noninvariance) for race and ethnicity on three ADOS items. Item-level bias was not apparent across gender. Although the magnitude of bias was small, our findings highlight the need to reevaluate norms and operational definitions used in assessments to increase ASD diagnostic accuracy among culturally-diverse groups.     

STAF score is a new simple approach for diagnosing cardioembolic stroke

Background and purpose: Detecting cardioembolic stroke soon after acute cerebral ischemia has a major impact on secondary stroke prevention. Recently, the Score for the Targeting of Atrial Fibrillation (STAF) was introduced to identify stroke patients at risk of atrial fibrillation. However, whether the STAF score could be a useful approach to differentiate cardioembolic stroke from other stroke subtypes is unclear. Methods: Consecutive patients with acute ischemic stroke that were admitted to our stroke center were enrolled. Each patient was assessed (age, baseline National Institutes of Health Stroke Scale, left atrial dilatation and absence of vascular etiology) to calculate the STAF score. A follow-up visit was conducted for each patient during hospitalization to determine the diagnosed stroke etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Results: The median and interquartile range of the STAF score was significantly higher in the cardioembolic than in the non-cardioembolic group [6 (2) vs. 2 (3), p < 0.001]. The discriminating ability of the STAF score model was good as demonstrated by the receiver operating characteristic curve. The area under the curve (AUC) of STAF score (AUC = 0.98; 95% CI, 0.96–0.99) was significantly greater than B-type natriuretic peptide (AUC = 0.87; 95% CI, 0.83–0.91) (p < 0.05). The optimal STAF cut-off value was ≥ 5, which diagnosed cardioembolic stroke with a sensitivity of 90% and specificity of 95%. Conclusions: The STAF score is a simple and accurate tool that can discriminate the cardioembolic stroke from other types during hospitalization for acute ischemic stroke.     

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.Electronic supplementary materialThe online version of this article (10.1007/s12264-021-00662-3) contains supplementary material, which is available to authorized users.